Gasotransmitter CO Attenuates Bleomycin-Induced Fibroblast Senescence via Induction of Stress Granule Formation.
Gasotransmitter CO Attenuates Bleomycin-Induced Fibroblast Senescence via Induction of Stress Granule Formation.
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DOI：
10.1155/2021/9926284
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发表时间：
2021
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Chen Y;Jiang F;Kong G;Yuan S;Cao Y;Zhang Q;Wang Q;Liu L
细胞衰老被认为是增殖细胞经历永久生长停滞的现象。随着时间的推移，衰老细胞的积累会变得有害，并导致疾病和生理衰退。纤溶酶原激活物抑制剂（派-1）被认为是细胞衰老的重要标志物和介质。应激颗粒（SG）的形成可以通过隔离派-1来防止衰老，我们以前认为外源性一氧化碳（CO）可以通过整合应激反应（ISR）诱导SG的组装。虽然已知CO具有抗炎、抗氧化和抗凋亡的特性，但其是否具有抗衰老作用仍不清楚。在这里，为了解决CO诱导的SG是否可以防止细胞衰老，我们首先用博来霉素（BLM）处理肺成纤维细胞以建立DNA损伤诱导的细胞衰老，并通过SA-β-gal染色、免疫荧光、qRT-PCR和Western印迹测定观察到衰老的几个标志的显著增加。然而，前和后处理的CO可以显着减弱这些衰老表型。根据我们的免疫荧光结果，CO诱导的SG可以通过隔离派-1来抑制BLM诱导的细胞衰老，而ISR抑制剂（ISRIB）的共同处理后，由于SG组装的抑制，它被取消。总的来说，我们的研究结果提出了一种新的作用，CO抑制博莱霉素诱导的肺成纤维细胞衰老通过组装的SG。
Cellular senescence is recognized as a phenomenon wherein a proliferative cell undergoes a permanent growth arrest. The accumulation of senescent cells over time can become harmful and result in diseases and physiological decline. Plasminogen activator inhibitor (PAI-1) is considered as a critical marker and mediator of cellular senescence. The formation of stress granules (SGs) could prevent senescence through the sequestration of PAI-1, and we previously suggested that exogenous carbon monoxide (CO) could induce SG assembly via integrated stress response (ISR). Although CO is known to possess anti-inflammatory, antioxidative, and antiapoptotic properties, whether it exerts antisenescent effect is still not well defined. Here, to address whether CO-induced SGs could protect against cellular senescence, we first treated lung fibroblasts with bleomycin (BLM) to establish DNA damage-induced cellular senescence, and observed a significant increase of several hallmarks of senescence through SA-β-gal staining, immunofluorescence, qRT-PCR, and Western blot assay. However, pre- and posttreatment of CO could remarkably attenuate these senescent phenotypes. According to our immunofluorescence results, CO-induced SGs could inhibit BLM-induced cellular senescence via sequestration of PAI-1, while it was abolished after the cotreatment of ISR inhibitor (ISRIB) due to the inhibition of SG assembly. Overall, our results proposed a novel role of CO in suppressing bleomycin-induced lung fibroblast senescence through the assembly of SGs.
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DOI：
10.1096/fj.201700709rr
发表时间：
2018-05
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Joe Y;Kim S;Kim HJ;Park J;Chen Y;Park HJ;Jekal SJ;Ryter SW;Kim UH;Chung HT
通讯作者：
Chung HT
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
8.8
作者：
Joe, Yeonsoo;Chen, Yingqing;Chung, Hun Taeg
通讯作者：
Chung, Hun Taeg
影响因子：
13.8
作者：
Kedersha, Nancy;Ivanov, Pavel;Anderson, Paul
通讯作者：
Anderson, Paul
影响因子：
4.8
作者：
Chen, Yingqing;Park, Hyeok-Jun;Chung, Hun Taeg
通讯作者：
Chung, Hun Taeg